Saturday, February 23, 2013

Dr. Burks' Presentation at AAAAI: Related Tweets

So for those of you who are not obsessed with research, this weekend is the annual AAAAI meeting down in San Antonio. A number of immunologists and allergists tweet during the presentations to give those of us who are not lucky enough to attend a glimpse of the presentations.

This morning was Dr. Wesley Burks' highly anticipated talk: Immune Tolerance and Allergy: Can We Produce True Tolerance? Here's what the various tweeters had to say:
Several studies now indicate that food allergy is related to defective T regulatory response” Anne Ellis, M.D ‏@DrAnneEllis
Some studies suggest that when peanut tolerance develops, existing cells do not change, but rather, new populations of cells arise. Peripheral t cell tolerance is key.  Children who have outgrown non IgE-mediated milk allergy demonstrate detectable T regulatory activity. Sakina Bajowala, M.D @allergistmommy
So these are things I've touched on in other columns. Somehow, a child's immune system gets off track when they're first born and develops an immune response that's similar to what the body uses to react to parasites (T2) rather than one that see proteins as harmless (T1).

The $64,000 question is: what, exactly, are these OIT trials (and, by extension, my son's FAHF-2 trial) actually doing? Are they changing the way the body responds? Or are they simply "stretching the balloon" as far as possible, but leaving the maladaptive underlying response intact?

This is important because, if the immune system is really not being changed, then it may be that desensitization and not true tolerance is the best we can hope for.
Allergic individuals form peanut-specific IgE, non-allergic form peanut specific IgG - IgG is a Normal response to a foreign protein. True Peanut allergic patients - their peanut specific IgE continues to rise with ongoing avoidance. Anne Ellis, M.D ‏@DrAnneEllis
Peanut OIT changes antigen specific Tregs and suppresses Th2 response to peanut. Sakina Bajowala, M.D ‏@allergistmommy

So it does appear that these studies are doing something to really change the immune system. That's positive, as there's more hope for true tolerance. It's also important to note that this idea of waiting for IgE levels to fall may not really be the signal for tolerance, as levels generally continue to rise as long as peanut is being avoided. How do the current studies do with regard to inducing desensitization?Assuming it works, how long does it last? Who does it work for?
Burks' studies: OIT for peanut lead to passing a 5000mg challenge while SLIT was only 1000mg. Participants in OIT trials-only 25% passed an oral challenge 4 weeks post treatment discontinuation c/w 75% while still on treatment. Anne Ellis, M.D ‏@DrAnneEllis
41% pts appear to be tolerant after 1-3 years of peanut immunotherapy Matthew Bowdish, M.D ‏@MatthewBowdish
Burks: Peanut OIT - those who developed tolerance had lower baseline PN IgE than those who did not. Dr Melinda Rathkopf ‏@mrathkopf
So there does seem to be a difference in the kids who will respond to the therapy and those who won't. Longer therapy is better. More direct therapy (OIT) works better than smaller doses (SLIT). And, it appears to last for 4 out of 10 kids if it's kept up over time. However, Burks' assessment of all this is:
Critical gaps in OIT/SLIT for food mean its not ready for routine clinical use. David Fischer, MD ‏@IgECPD
A future question to be answered: would starting with younger kids who presumably have more malleable immune systems improve the response? In order to find out:
Impact peanut study. 2000mg maintenance dose for 4 years. Multicenter study. Sakina Bajowala, M.D ‏@allergistmommy
W Burks announces IMPACT study targeting 140 children under 4 with  to peanut.  @WayneShreffler
Burks' next study "Impact" - peanut allergic kids aged 1- 4 to see if OIT will be more likely to induce tolerance if started earlier. Anne Ellis, M.D ‏@DrAnneEllis
So...something to be on the lookout for if you have a child under the age of four and are just starting out on this fun journey.

What a wonderful glimpse into the #AAAAI world!  I am very grateful to these tweeters for sharing these conferences as they occur.

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